The mastocytoses result from abnormal proliferations of mast cells and display cutaneous and/or systemic forms. This disease(s) affords a unique setting for clarifying the specific role of mast cells in the release of various biologically active mediators. In addition, the nature of the mast cell proliferations (neoplastic or hyperplastic) remains unclear. Recent advances in defining normal mast cell heterogeneity as a function of body site have not been applied systematically to the abnormal mast cells of the mastocytoses. Clarification of the phenotypic patterns will provide insight into the neoplastic or hyperplastic nature of the infiltrates in mastocytosis and provide clues regarding the importance of tissue environment in determining heterogeneity. To achieve these goals, we plan to biopsy skin lesions in patients with mastocytosis. In the tissues we will determine the distribution as well as ultrastructural and immunocytochemical phenotype of the abnormal mast cells. Furthermore, as techniques and reagents develop, in situ hybridization will be employed to confirm the presence or absence of specific cytokine mRNA in mast cells. Endothelial activation will be assayed to assess a probable site of action of these cytokines. Controls will include identical studies of mast cells in normal tissues and clinically similar dermatitides. Findings will be quantitated and apparent differences tested for statistical significance.